APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC

NCT03655613 | Terminated Phase 1

• 1 other identifier: APOLLO
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 9

Brief Summary

Study Design and Investigational Plan: This is an open-label Phase 1/2 study to assess the safety and tolerability of combination PD-1 inhibitor (APL-501 or nivolumab) administered concomitantly with c-Met inhibitor (APL-101), to determine the recommended Phase 2 dose of the combination, and to obtain preliminary efficacy in HCC or RCC subjects with advanced or metastatic disease that have not been previously treated with a PD 1 inhibitor or a c-Met inhibitor. HCC subjects will receive the combination APL-501 plus APL-101 while RCC subjects will receive the combination nivolumab plus APL-101. In Phase 1, mandatory archival or fresh tumor biopsies will be collected. In Phase 2, a mandatory fresh tumor biopsy will be required for study entry and another fresh biopsy will be collected between Cycles 2 and 4. The frequency of administration of PD-1 inhibitors will be every 2 weeks starting in Cycle 1 on Day 8 and Day 22 of a 35-day cycle with all subsequent cycles on Day 1 and Day 15 of 28-day cycles. APL-101 will be administered orally every 12 hours continuously on an empty stomach.

Conditions

Hepatocellular Carcinoma; Renal Cell Carcinoma

Keywords

Immunotherapy; PD-1 inhibitor; c-Met inhibitor

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicities (Phase 1)

  Dose limiting toxicities (DLTs)

  Cycle 1 (up to 35 days)

Secondary Outcomes (6)

• Adverse events

  First dose up to 90 days post last dose (up to approximately 2 years)

• Drug discontinuation due to adverse events

  First dose up to 90 days post last dose (up to approximately 2 years)

• Overall Response Rate

  Duration of study, performed at baseline, then every 8 weeks until objective disease progression (up to approximately 2 years)

• Time to Response

  Duration of study, first dose to first response (up to approximately 2 years)

• Progression Free Survival

  Duration of study, performed at baseline, then every 8 weeks until objective disease progression at 6, 12, 18 and 24 months (up to approximately 2 years)

Study Arms (2)

Arm A: Hepatocellular Carcinoma

EXPERIMENTAL

PD-1 inhibitor (APL-501) 3 mg/kg intravenously every 2 weeks + c-Met inhibitor (APL-101) 150 mg or 200 mg administered twice daily continuously until documented disease progression, discontinuation due to toxicity withdrawal of consent or the study ends

Biological: APL-501; Drug: APL-101

Arm B: Renal Cell Carcinoma

EXPERIMENTAL

PD-1 inhibitor (nivolumab) 3 mg/kg or 240 mg intravenously every 2 weeks + c-Met inhibitor (APL-101) 300 mg or 400 mg administered twice daily continuously until documented disease progression, discontinuation due to toxicity withdrawal of consent or the study ends

Drug: APL-101; Biological: Nivolumab

Interventions

APL-501 BIOLOGICAL

Humanized IgG4 monoclonal antibody against programmed death receptor-1 (PD-1)

Also known as: genolimzumab, GB226, CBT-501

Arm A: Hepatocellular Carcinoma

APL-101 DRUG

Oral specific c-Met inhibitor

Also known as: bozitinib, vebreltinib, CBT-501

Arm A: Hepatocellular Carcinoma; Arm B: Renal Cell Carcinoma

Nivolumab BIOLOGICAL

Fully human IgG4 monoclonal antibody against PD-1

Also known as: Opdivo

Arm B: Renal Cell Carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent.
• Men and women 18 years of age or older.
• Histologically confirmed advanced or metastatic hepatocellular carcinoma that progressed while receiving at least one previous line of systemic therapy, including sorafenib, or who are intolerant of or refused sorafenib treatment following progression on standard therapy including surgical and/or local regional therapies, or standard therapy considered ineffective, intolerable, or inappropriate or for which no effective standard therapy is available.
• Histologically confirmed advanced or metastatic renal cell carcinoma with clear cell component who received one or two prior lines of antiangiogenic therapy in addition to no more than three previous regimens of systemic therapy including cytokines and cytotoxic chemotherapy agents.
• Disease according to irRECIST that can be reliably and consistently followed.
• Documented disease progression during or after the last treatment regimen and within 6 months before study enrollment.
• Tumor amenable to tumor biopsy and subject agreeable to tumor biopsy at study entry and during therapy with study treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Acceptable organ function.

You may not qualify if:

• History of severe hypersensitivity to mAbs, excipients of the APL-501, nivolumab, or APL-101.
• History of receiving treatment with any c-Met signaling pathway inhibitor (marketed or investigational agents).
• Prior therapy with anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-stimulation pathways).
• Unwilling to swallow orally administered medication whole.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., Crohn's, ulcerative colitis, active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
• Documented and/or known history of human immunodeficiency virus (HIV) for HCC and RCC subjects, or historical seropositive results consistent with active infection for hepatitis C virus (HCV) or hepatitis B virus (HBV) (RCC only).
• HCC subjects receiving active antiviral therapy for HCV.
• Active co-infection with HBV and HCV.
• Active co-infection with HBV and hepatitis D virus.

Sponsors & Collaborators

• Apollomics (Australia) Pty. Ltd.: lead
• Apollomics Inc. (formerly CBT Pharmaceuticals, Inc.): collaborator
• Novotech (Australia) Pty Limited: collaborator

Study Sites (9)

Border Medical Oncology Research Unit

Albury, New South Wales, 2640, Australia

Location

Macquarie University

Sydney, New South Wales, 2109, Australia

Location

Crown Princess Mary Cancer Centre

Westmead, New South Whales, 2145, Australia

Location

Ashford Cancer Center

Adelaide, South Australia, 5037, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Sunshine Hospital

Saint Albans, Victoria, 3021, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Afffinity Clinical Research

Perth, Western Australia, 6018, Australia

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Related Links

• Company website for Apollomics Inc.

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Carcinoma, Renal Cell

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Scott Houston

  Apollomics (Australia) Pty. Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: (Phase 1) 3+3 dose escalation (Phase 2) Simon two-stage Minimax design

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: August 31, 2018
• Study Start: September 5, 2018
• Primary Completion: December 15, 2021
• Study Completion: December 15, 2021
• Last Updated: May 6, 2022

Record last verified: 2022-05

Locations

AU (8); NZ (1)